HLA-DM mediates peptide exchange by interacting transiently and repeatedly with HLA-DR1

Kedar Narayan, Katherine W. Su, Chih Ling Chou, Stanislav Khoruzhenko, Scheherazade Sadegh-Nasseri

Research output: Contribution to journalArticlepeer-review

Abstract

The peptide editor HLA-DM (DM) catalyzes the exchange of peptides bound to MHC class II molecules within antigen presenting cells by generating a "peptide-receptive" MHC class II conformation (MHCreceptive) to which peptides readily bind and rapidly unbind. While recent work has uncovered the determinants of DM recognition and effector functions, the nature of MHCreceptive and its interaction with DM remains unclear. Here, we show that DM induces but does not stabilize MHCreceptive in the absence of peptides. We demonstrate that DM is out-competed by certain superantigens, and increasing solvent viscosity inhibits DM-induced peptide association. We suggest that DM mediates peptide exchange by interacting transiently and repeatedly with MHC class II molecules, continually generating MHCreceptive. The simultaneous presence of peptide and DM in the milieu is thus crucial for the efficient generation of specific peptide-MHC class II complexes over time.

Original languageEnglish (US)
Pages (from-to)3157-3162
Number of pages6
JournalMolecular Immunology
Volume46
Issue number15
DOIs
StatePublished - Sep 1 2009

Keywords

  • Antigen presentation
  • Antigen processing
  • Diffusion
  • HLA-DM
  • Kinetics
  • Peptide
  • Peptide-receptive HLA-DR
  • Superantigen
  • Surface plasmon resonance
  • Viscosity

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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